Estimating prevalence of distant metastatic breast cancer: a means of filling a data gap

PURPOSE: To develop and validate a method for estimating numbers of people with distant cancer metastases, for evidence-based service planning. METHODS: Estimates were made employing an illness-death model with distant metastatic cancer as the illness state- and site-specific mortality as an outcome, using MIAMOD software. To demonstrate the method, we estimated numbers of females alive in Australia following detection of distant metastatic breast cancer during 1980-2004, using data on patient survival from an Australian population-based cancer registry. We validated these estimates by comparing them with direct prevalence counts. RESULTS: Relative survival at 10 years following detection of distant metastases was low (5-20 %), with better survival experienced by: (1) females where distant metastatic disease was detected at initial diagnosis rather than subsequently (e.g., at recurrence); (2) those diagnosed in more recent calendar years; and (3) younger age groups. For Australian females aged less than 85 years, the modeled cumulative risk of detection of distant metastatic breast cancer (either at initial diagnosis or subsequently) declined over time, but numbers of cases with this history rose from 71 per 100,000 in 1980 to 84 per 100,000 in 2004. The model indicated that there were approximately 3-4 prevalent distant metastatic breast cancer cases for every breast cancer death. Comparison of estimates with direct prevalence counts showed a reasonable level of agreement. CONCLUSIONS: The method is straightforward to apply and we recommend its use for breast and other cancers when registry data are insufficient for direct prevalence counts. This will provide estimates of numbers of people who would need ongoing medical surveillance and care following detection of distant metastase

Study of CAPE effect on apoptosis induction in AGS human gastric cancer cell line

Background: Propolis is a natural product of bee and caffeic acid phenethyl ester (CAPE) is a pharmacologically important product of propolis. Objectives: The aim of this study was to investigate the effect of CAPE on apoptosis induction in AGS human gastric cancer cells. Materials and Methods: The cytotoxic effects of CAPE at different concentrations were investigated on AGS cells viability after 24 hours treatment by MTT assay. To measure the effect of CAPE on apoptosis induction, AGS cells were treated with CAPE for 24 hours and investigated by FITC Annexin V/PI staining using flow cytometry. Results: CAPE prevented growth and proliferation of AGS human gastric cancer cell line in a concentration-dependent manner with an IC50 of approximately 60 μM by a 24-hour treatment. Also CAPE caused increased induction of apoptosis in AGS cells from 1.37 % in control cells to 21.76 % in treated cells with 30 μM CAPE. Conclusions: CAPE prevents growth and proliferation of AGS human gastric cancer cell line through inducing programmed cell death in AGS cells. Therefore, CAPE could be helpful for developing chemotherapeutic agents or as an adjuvant for human gastric cancer treatment. © 2016, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences

Pancreatectomy is underused in NSW regions with low institutional surgical volumes: A population data linkage study

© 2017 AMPCo Pty Ltd. Produced with Elsevier B.V. All rights reserved. Objective: To examine differences in the proportions of people diagnosed with pancreatic cancer who underwent pancreatectomy, post-operative outcomes and 5-year survival in different New South Wales administrative health regions of residence. Design, setting and participants: Retrospective analysis of NSW data on pancreatic cancer incidence and surgery, 2005e2013. Main outcome measures: The proportion of newly diagnosed patients with pancreatic cancer who were resected in each region; 90-day post-operative mortality; one-year post-operative survival; 5-year post-diagnosis survival. Results: 14% of people diagnosed with pancreatic cancer during 2010e2013 (431 of 3064) underwent pancreatectomy, an average of 108 resections per year. After adjusting for age, sex and comorbidities, the proportion that underwent resection varied significantly between regions, ranging between 8% and 21% (P<0.001). Higher resection rates were not associated with higher post-operative 90-day mortality or lower one-year survival (unadjusted and risk-adjusted analyses). Higher resection rates were associated with higher 5-year post-diagnosis survival: the mean survival in regions with resection rates below 10% was 3.4%, compared with 7.2% in regions with rates greater than 15% (unadjusted and adjusted survival analyses; P<0.001). There was a positive association between regional resection rate and the pancreatectomy volume of hospitals during 2005e2009. An additional 32 people would be resected annually if resection rates in low rate regions were increased to the 80th percentile regional resection rate (18%). Conclusion: There is significant geographic variation in the proportion of people with pancreatic cancer undergoing pancreatectomy, and the 5-year survival rate is higher in regions where this proportion is higher

Epidemiological analysis of tongue cancer in South Australia for the 24-year period, 1977-2001

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Tongue cancer (141 ICD-9) is the most common intra-oral malignancy in Western countries. In recent decades, reported tongue cancer incidence and mortality rates have increased both in Europe and in the United States, whilst survival has not improved. This study aimed to determine the epidemiology and survival trends of tongue cancer in South Australia over the 24-year period from 1977 to 2001. Methods: Population-based data for tongue cancer were provided by the Central Cancer Registry Unit of the Epidemiology Branch of the South Australian Department of Health. Age-standardized incidence and mortality rates for males and females were calculated. Kaplan-Meier survival analysis was conducted according to time periods, age, sex and tongue sub-sites. Cox regression analysis was used to determine factors that influenced survival. Results: During this 24-year period, 611 cases of tongue cancer (398 males, 213 females) were reported, the majority of which were squamous cell carcinomas. The most common age of diagnosis was 65–69 years in males and 60–64 years in females. Fifty cases (8.18 per cent of all tongue cancer cases) occurred in patients 40 years or younger. The most common cancer sub-sites reported were ‘unspecified site’ (48.45 per cent), lateral border (25.53 per cent) and base (18.49 per cent) of the tongue. The agestandardized incidence and mortality rates for males and females in South Australia were relatively low and stable, and there was no significant improvement in survival of tongue cancer over this period. Significant predictors for survival were sex, age and tongue sub-sites, with male, advanced age and base of tongue associated with poorer survival. Conclusions: Tongue cancer is an important health issue associated with poor survival. Early detection and diagnosis is important in order to improve survival rate for this malignancy.L Lam, RM Logan and C Luk

Breast screening attendance of Aboriginal and Torres Strait Islander women in the Northern Territory of Australia

Objective: To compare breast screening attendances of Indigenous and non-Indigenous women. Methods: A total of 4,093 BreastScreen cases were used including 857 self-identified Indigenous women. Chi-squared analysis compared data between Indigenous and non-Indigenous women. Logistic regression was used for groupings based on visits-to-screening frequency. Odds ratios and 95% confidence intervals were calculated for associations with low attendance. Results: Indigenous women were younger and had fewer visits to screening compared with non-Indigenous women. Non-English speaking was mainly associated with fewer visits for Indigenous women only (OR 1.9, 95%CI 1.3-2.9). Living remotely was associated with fewer visits for non-Indigenous women only (OR 1.3, 95%CI 1.1-1.5). Shared predictors were younger age (OR 12.3, 95%CI 8.1-18.8; and OR 11.5, 95%CI 9.6-13.7, respectively) and having no family history of breast cancer (OR 2.1, 95%CI 1.3-3.3; and OR 1.8, 95%CI 1.5-2.1, respectively). Conclusions: Factors associated with fewer visits to screening were similar for both groups of women, except for language which was significant only for Indigenous women, and remoteness which was significant only for non-Indigenous women. Implications for public health: Health communication in Indigenous languages may be key in encouraging participation and retaining Indigenous women in BreastScreen; improving access for remote-living non-Indigenous women should also be addressed

Predicting postoperative complications for gastric cancer patients using data mining

Gastric cancer refers to the development of malign cells that can grow in any part of the stomach. With the vast amount of data being collected daily in healthcare environments, it is possible to develop new algorithms which can support the decision-making processes in gastric cancer patients treatment. This paper aims to predict, using the CRISP-DM methodology, the outcome from the hospitalization of gastric cancer patients who have undergone surgery, as well as the occurrence of postoperative complications during surgery. The study showed that, on one hand, the RF and NB algorithms are the best in the detection of an outcome of hospitalization, taking into account patients’ clinical data. On the other hand, the algorithms J48, RF, and NB offer better results in predicting postoperative complications.FCT - Fundação para a Ciência e a Tecnologia (UID/CEC/00319/2013

PB1-F2 Proteins from H5N1 and 20th Century Pandemic Influenza Viruses Cause Immunopathology

With the recent emergence of a novel pandemic strain, there is presently intense interest in understanding the molecular signatures of virulence of influenza viruses. PB1-F2 proteins from epidemiologically important influenza A virus strains were studied to determine their function and contribution to virulence. Using 27-mer peptides derived from the C-terminal sequence of PB1-F2 and chimeric viruses engineered on a common background, we demonstrated that induction of cell death through PB1-F2 is dependent upon BAK/BAX mediated cytochrome c release from mitochondria. This function was specific for the PB1-F2 protein of A/Puerto Rico/8/34 and was not seen using PB1-F2 peptides derived from past pandemic strains. However, PB1-F2 proteins from the three pandemic strains of the 20th century and a highly pathogenic strain of the H5N1 subtype were shown to enhance the lung inflammatory response resulting in increased pathology. Recently circulating seasonal influenza A strains were not capable of this pro-inflammatory function, having lost the PB1-F2 protein's immunostimulatory activity through truncation or mutation during adaptation in humans. These data suggest that the PB1-F2 protein contributes to the virulence of pandemic strains when the PB1 gene segment is recently derived from the avian reservoir

Female Fertility Affects Men's Linguistic Choices

We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women

Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047)

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT (‘Adjuvant-RT’) or an observation policy with salvage RT for PSA failure (‘Salvage-RT’) defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047

Natural killer cells are crucial for the efficacy of Icon (factor VII/human IgG1 Fc) immunotherapy in human tongue cancer

<p>Abstract</p> <p>Background</p> <p>Icon is a novel, dual neovascular- and cancer cell-targeting immunotherapeutic agent and has shown efficacy in the treatment of cancer, wet form macular degeneration and endometriosis. However, its underlying mechanism remains to be investigated. The objective of this study is to elucidate the mechanism of Icon immunotherapy in cancer using a squamous carcinoma human tongue cancer line TCA8113 <it>in vitro </it>and <it>in vivo </it>in severe combined immunodeficiency (SCID) mice.</p> <p>Results</p> <p>We showed that Icon, as a chimeric factor VII and human IgG1 Fc immunoconjugate, could separately induce murine natural killer (NK) cells and activate complement to kill TCA8113 cancer cells <it>in vitro </it>via antibody dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, Icon-NK ADCC had a significantly stronger effect than that of Icon-CDC. Moreover, Icon could completely eradicate established human tongue tumour xenografts <it>in vivo </it>in the CB-17 strain of SCID mice that have functional NK cells at a normal level, whereas it was less effective in SCID/Beige mice that do not have functional NK cells.</p> <p>Conclusions</p> <p>We conclude that NK cells are crucial for the efficacy of Icon immunotherapy in the treatment of cancer. The results also suggest that impaired NK level/activity could contribute to the resistance to therapeutic antibodies that are currently under investigation in preclinical and clinical studies.</p